Inhibition of HIV-1 Infection by Potent Metallocene Conjugated Peptide Through Conformational Entrapment of Envelope GP120
The invention provides a peptide triazole conjugate and derivatives thereof, and methods of its use.
1 . A peptide triazole conjugate comprising a peptide component comprising the sequence INNIPWS (SEQ ID NO. 1), wherein the proline in SEQ ID NO. 1 is modified according to Formula I:
wherein R is a bulky aromatic group.
2 . The peptide triazole conjugate of claim 1 , wherein said bulky aromatic group is selected from the group consisting of a naphthyl group; a para-alkyl-substituted phenyl, wherein the alkyl is methyl or ethyl; 2-phenylethyl; and a metallocene.
3 . The peptide triazole conjugate of claim 1 , wherein said bulky aromatic group is a metallocene.
4 . The peptide triazole conjugate of claim 3 , wherein said metallocene is ferrocene.
5 . (canceled)
6 . The peptide triazole conjugate of claim 1 , wherein said peptide component further comprises residues 1 and 9-12 of the sequence RINNIPWSEAMM (SEQ ID NO. 2) flanking the N-terminus and C-terminus respectively of SEQ ID No. 1.
7 - 9 . (canceled)
10 . A pharmaceutical composition comprising a peptide triazole conjugate and a pharmaceutically acceptable carrier,
wherein said peptide triazole conjugate comprises a peptide component comprising the sequence INNIPWS (SEQ ID NO. 1), wherein the proline in SEQ ID NO. 1 is modified according to Formula I:
wherein R is a bulky aromatic group.
11 . The pharmaceutical composition of claim 10 , wherein said bulky aromatic group is selected from the group consisting of a naphthyl group; a para-alkyl-substituted phenyl, wherein the alkyl is methyl or ethyl; 2-phenylethyl; and a metallocene.
12 . (canceled)
13 . The pharmaceutical composition of claim 10 , wherein R is ferrocene.
14 . The A pharmaceutical composition of claim 10 , wherein said
further comprises residues 1 and 9-12 of the sequence RINNIPWSEAMM (SEQ ID NO. 2) flanking the N-terminus and C-terminus respectively of SEQ ID NO. 1.
15 - 17 . (canceled)
18 . The pharmaceutical composition of claim 10 further comprising cyanovirin-N or a functional derivative thereof.
19 . (canceled)
20 . The pharmaceutical composition of claim 18 , wherein said peptide triazole conjugate is linked to said cyanovirin-N or a functional derivative thereof.
21 . The pharmaceutical composition of claim 18 , wherein the N-terminal residue of said peptide triazole conjugate is covalently linked to the C-terminal residue of said cyanovirin-N or functional derivative thereof.
22 - 31 . (canceled)
32 . A method of treating HIV, said method comprising administering a therapeutically effective amount of a peptide triazole conjugate to an individual diagnosed with HIV, wherein said peptide triazole conjugate comprises a peptide component comprising the sequence INNIPWS (SEQ ID NO. 1), wherein the proline in SEQ ID NO. 1 is modified according to Formula I:
wherein R is a bulky aromatic group.
33 . The method of claim 32 , wherein said bulky aromatic group is selected from the group consisting of a naphthyl group; a para-alkyl-substituted phenyl, wherein the alkyl is methyl or ethyl; 2-phenylethyl; and a metallocene.
34 . The method of claim 32 , wherein said bulky aromatic group is a metallocene.
35 . The method of claim 34 , wherein said metallocene is ferrocene.
36 - 37 . (canceled)
38 . The method of claim 32 , wherein said pharmaceutical composition further comprises cyanovirin-N or a functional derivative thereof.
39 . The method of claim 32 wherein a peptide component further comprises residues 1 and 9-12 of the sequence RINNIPWSEAMM (SEQ ID NO. 2) flanking the N-terminus and C-terminus respectively of SEQ ID NO. 1.
40 - 45 . (canceled)
46 . A method of reducing the risk of HIV infection, said method comprising administering a therapeutically effective amount of a peptide triazole conjugate to an individual at risk of HIV exposure, wherein said peptide triazole conjugate comprises a peptide component comprising the sequence INNIPWS (SEQ ED NO. 1), wherein the proline in SEQ ID NO. 1 is modified according to Formula I:
wherein R is a bulky aromatic group.
47 . The method of claim 46 , wherein said bulky aromatic group is selected from the group consisting of a naphthyl group; a para-alkyl-substituted phenyl, wherein the alkyl is methyl or ethyl; 2-phenylethyl; and a metallocene.
48 . The method of claim 46 , wherein said bulky aromatic group is a metallocene.
49 . The method of claim 48 , wherein said metallocene is ferrocene.
50 - 51 . (canceled)
52 . The method of claim 46 , wherein said pharmaceutical composition further comprises cyanovirin-N or a functional derivative thereof.
53 . (canceled)
54 . The method of claim 46 wherein peptide component further comprises residues 1 and 9-12 of the sequence RINNIPWSEAMM (SEQ ID NO. 2) flanking the N-terminus and C-terminus respectively of SEQ ID NO. 1.
55 - 61 . (canceled)
62 . A method of isolating a viral envelope protein gp120, said method comprising contacting a solid phase matrix with a sample comprising gp120, wherein a peptide triazole conjugate comprising a peptide component comprising the sequence INNIPWS (SEQ ID NO. 1), wherein the proline of SEQ ID NO. 1 is modified according to Formula I:
wherein R is a bulky aromatic group, is linked to said solid phase matrix, wherein said gp120 binds to said peptide triazole conjugate thereby partitioning said sample into a bound phase and an unbound phase; and
separating said unbound phase from said unbound phase, thereby isolating said gp120.
63 . (canceled)
64 . The method of 62, wherein said gp120 is associated with HIV-1 viral particles.
65 - 66 . (canceled)